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N J Beauchamp

Publications and source records attributed to N J Beauchamp.

At least 37 records · Page 2Linked to original sources
PubMed2000

Diffusion-weighted MRI and proton MR spectroscopic imaging in the study of secondary neuronal injury after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Cerebral ischemia has been proposed as contributing mechanism to secondary neuronal injury after intracerebral hemorrhage (ICH). Possible tools for investigating this hypothesis are diffusion-weighted (DWI) and proton magnetic resonance spectroscopic imaging ((1)H-MRSI). However, magnetic field inhomogeneity induced by paramagnetic blood products may prohibit the application of such techniques on perihematoma tissue. We report on the feasibility of DWI and (1)H-MRSI in the study of human ICH and present preliminary data on their contribution to understanding perihematoma tissue functional and metabolic profiles. METHODS: Patients with acute supratentorial ICH were prospectively evaluated using DWI and (1)H-MRSI. Obscuration of perihematoma tissue with both sequences was assessed. Obtainable apparent diffusion coefficient (Dav) and lactate spectra in perihematoma brain tissue were recorded and analyzed. RESULTS: Nine patients with mean age of 63.4 (36 to 87) years were enrolled. Mean time from symptom onset to initial MRI was 3.4 (1 to 9) days; mean hematoma volume was 35.4 (5 to 80) cm(3). Perihematoma diffusion values were attainable in 9 of 9 patients, and (1)H-MRSI measures were obtainable in 5 of 9 cases. Dav in perihematoma regions was 172.5 (120.0 to 302.5)x10(-5) mm(2)/s and 87.6 (76.5 to 102.1)x10(-5) mm(2)/s in contralateral corresponding regions of interest (P=0.002). One patient showed an additional area of reduced Dav with normal T(2) intensity, which suggests ischemia. (1)H-MRSI revealed lactate surrounding the hematoma in 2 patients. CONCLUSIONS: DWI and (1)H-MRSI can be used in the study of ICH patients. Our preliminary data are inconsistent with ischemia as the primary mechanism for perihematoma tissue injury. Further investigation with advanced MRI techniques will give a clearer understanding of the role that ischemia plays in tissue injury after ICH.

Adult↗
PubMed2000

Major structural defects in the antithrombin gene in four families with type I antithrombin deficiency--partial/complete deletions and rearrangement of the antithrombin gene.

The molecular basis of quantitative antithrombin deficiency was investigated in four families predicted to have major antithrombin gene rearrangements. A 1,442 bp deletion and insertion of the sequence 5'T(n = 38-40)GAGACG was characterised in one case. Sequence surrounding the breakpoints contained two perfect, and one imperfect, inverted repeats which may have mediated formation of a stem loop structure on one strand during DNA replication potentiating the deletion. A 9,219 bp deletion spanning introns 2 to 5 was identified in a second family. The identical 6 bp sequence was upstream of each breakpoint and the 5' breakpoint was located in a sequence of the Alu 3 repeat predicted to be susceptible to strand breakage during transcription. This may have promoted misalignment, and deletion, of one of the repeats and the intervening DNA. A novel 1.8 kb antithrombin gene fragment was present in DNA digests from affected members of the third family suggesting a partial antithrombin gene duplication event while in the remaining family, evidence supporting a complete gene deletion was obtained.

Adolescent↗
PubMed1999

Recent advances in imaging of cerebrovascular disease.

The recent advances made in CT and MR imaging have led to increased accuracy in making a number of diagnoses in the emergency room setting. Increasingly, radiologists are asked to perform these studies and accurately interpret the findings, which often have a dramatic impact on triaging and treatment of the patient. Future trials need to address further the relative merits of each of the techniques outlined previously in specific settings. In addition, given the increasing number of means of obtaining diagnostic information, cost effectiveness studies are needed to better formulate an appropriate algorithm for each diagnosis.

Cerebral Infarction↗
PubMed1999

Neurogenic ST depression in stroke.

BACKGROUND: Stroke is occasionally associated with ECG repolarization changes including ST depression. Recent evidence suggests a neurogenic contribution to these abnormalities in stroke patients. Animal studies implicate the insular cortex in cardiovascular control. We describe a patient with a left insular infarct and without cardiac or coronary artery disease, who developed ST depression indicating a neurogenic etiology. CASE DESCRIPTION: A 48 year-old female, with no risk factors for stroke, developed sudden expressive aphasia. MRI brain showed an infarct in the left insular cortex. Twenty-four hour Holter monitoring on the third day revealed transient ST depression more than 1.5 mm, which was not reproducible on subsequent monitoring. Transesophageal echo-cardiography (TEE) was normal. She had no cardiac symptoms and serial ECGs, cardiac enzymes (CKMB) and adenosine thallium scan were normal. To-date, there had been no cardiac events like congestive heart failure or myocardial ischemia. CONCLUSION: These findings suggest neurogenic ST depression is related to the left insular infarct in view of the normal adenosine thallium scan, non-reproducibility and evanescence of the ST segment changes and lack of associated cardiac symptoms. When neurogenic ST depression is combined with underlying coronary artery disease, it may adversely influence cardiac outcome after stroke.

Cerebral Cortex↗
PubMed1999

A decision guideline for emergency department utilization of noncontrast head computed tomography in HIV-infected patients.

OBJECTIVE: To determine which neurologic signs or symptoms are predictive of new focal lesions on head CT in HIV-infected patients. METHODS: Prospective study with convenience sample enrollment of HIV-infected patients who presented to a large inner-city university-based ED over an 11-month period. Patients were assessed using a standardized neurologic evaluation to ascertain whether they had developed new or changed neurologic signs or symptoms. Patients with any new or changed neurologic findings had a head CT scan in the ED. The association between individual complaints or findings and new focal lesions on head CT was assessed by univariate analysis, and sensitivity, specificity, and positive predictive values were calculated. Stepwise logistic regression analysis was then carried out to estimate the relative risk for those variables independently associated with new focal lesions on CT scans. A decision guideline was developed incorporating those variables. RESULTS: One hundred ten patients were identified as having new or changed neurologic signs or symptoms and had a head CT done in the ED. Twenty-seven patients (24%) had focal lesions on head CT, of which 19 (18%) were identified as new focal lesions; eight of these (7%) demonstrated a mass effect. Clinical findings most strongly associated with new focal findings on head CT were: 1) new seizure, relative risk (RR) = 73.5, 95% CI = 6.2 to 873.0; 2) depressed or altered orientation, RR = 39.1, 95% CI = 4.6 to 330.0; and 3) headache, different in quality, RR = 27.0, 95% CI = 3.2 to 230.1. Use of these three findings as a screen for ordering head CT in the ED would have identified 95% (18/19) of the patients with new focal intracranial lesions, and resulted in a 53% reduction in the number of head CTs ordered in the ED. Inclusion of one additional parameter (prolonged headache, > or =3 days), would have resulted in identification of 100% of all new focal lesions, with a 37% reduction in the number of head CTs ordered. Among those patients with new focal findings, 74% required emergent management (i.e., seizure control, IV antibiotics, IV steroids or surgery). The most common intracranial lesion among patients with CD4 counts less than 200 cells/microL was toxoplasmosis, while cerebrovascular accidents (ischemic or hemorrhagic) were most common in those with CD4 counts greater than 200 cells/microL. CONCLUSION: Specific clinical signs and symptoms were associated with the presence of new intracranial lesions in a group of HIV-infected patients who presented to the ED with neurologic complaints. These clinical findings can be incorporated into guidelines for determining the need for emergent head CT. Validation and widespread application of these guidelines could result in limiting the use of emergent neuroimaging to a more well-defined HIV-infected patient population.

AIDS Dementia Complex↗
PubMed1999

Imaging of acute cerebral ischemia.

Until recently, there was no efficacious treatment for acute cerebral ischemia. As a result, the role of neuroimaging and the radiologist was peripheral in the diagnosis and management of this disease. The demonstration of efficacy using thrombolysis has redefined this role, with the success of intervention becoming increasingly dependent on timely imaging and accurate interpretation. The potential benefits of intervention have only begun to be realized. In this State-of-the-Art review of imaging of acute stroke, the role of imaging in the current and future management of stroke is presented. The role of computed tomography is emphasized in that it is currently the most utilized technique, and its value has been demonstrated in prospective clinical trials. Magnetic resonance techniques are equally emphasized in that they have the potential to provide a single modality evaluation of tissue viability and vessel patency in an increasingly rapid evaluation.

Acute Disease↗
PubMed1998

Antithrombins Wibble and Wobble (T85M/K): archetypal conformational diseases with in vivo latent-transition, thrombosis, and heparin activation.

The inherent variability of conformational diseases is demonstrated by two families with different mutations of the same conserved aminoacid in antithrombin. Threonine 85 underlies the opening of the main beta-sheet of the molecule and its replacement, by the polar lysine, in antithrombin Wobble, resulted in a plasma deficiency of antithrombin with an uncharacteristically severe onset of thrombosis at 10 years of age, whereas the replacement of the same residue by a nonpolar methionine, antithrombin Wibble, gave near-normal levels of plasma antithrombin and more typical adult thromboembolic disease. Isolated antithrombin Wibble had a decreased thermal stability (Tm 56.2, normal 57.6 degreesC) but was fully stabilized by the heparin pentasaccharide (Tm 71.8, normal 71.0 degreesC), indicating that the prime abnormality is a laxity in the transition of the main sheet of the molecule from the 5- to 6-stranded form, as was confirmed by the ready conversion of antithrombin Wibble to the 6-stranded latent form on incubation. That this transition can occur in vivo was shown by the finding of nearly 10% of the proband's plasma antithrombin in the latent form and also, surprisingly, of small but definitive amounts of latent antithrombin in normal plasma. The latent transition will be predictably accelerated not only by gross mutations, as with antithrombin Wobble, to give severe episodic thrombosis, but also by milder mutations, as with antithrombin Wibble, to trigger thrombosis in the presence of other predisposing factors, including the conformational stress imposed by the raised body temperatures of fevers. Both antithrombin variants had an exceptional (25-fold) increase in heparin affinity and this, together with an increased inhibitory activity against factor Xa, provides evidence of the direct linkage of A-sheet opening to the conformational basis of heparin binding and activation.

Amino Acid Substitution↗
PubMed1998

Neurovascular applications of CT angiography.

CT angiography, which has important advantages over both MR and ultrasound, is rapidly becoming an important modality for noninvasive evaluation of the neurovasculature. This article discusses CT angiography techniques for imaging the neurovasculature, including spiral acquisition protocols and image processing techniques, with a focus on the use of volume rendering for three-dimensional visualization. The clinical results for CT angiography of the cervical carotid arteries, intracranial aneurysms, arteriovenous malformations, and emerging work in the evaluation of acute stroke are reviewed. Important areas of ongoing research also are described.

Aneurysm↗
PubMed1998

Aspirin use and incident stroke in the cardiovascular health study. CHS Collaborative Research Group.

BACKGROUND AND PURPOSE: Randomized clinical trials testing aspirin in relatively low-risk, middle-aged people have consistently shown small increases in stroke associated with aspirin use. We analyzed the relationship between the regular use of aspirin and incident ischemic and hemorrhagic stroke among people aged 65 years or older participating in the Cardiovascular Health Study. METHODS: We conducted a multivariate analysis of incident stroke rates in a prospectively assessed, observational cohort of 5011 elderly people followed for a mean of 4.2 years. RESULTS: Participants had a mean age of 72 years, and 58% were women. Twenty-three percent used aspirin frequently, and 17% used aspirin infrequently at study entry. Frequent aspirin use was associated with an increased rate of ischemic stroke compared with nonusers (relative risk= 1.6; 95% confidence interval [CI], 1.2 to 2.2; P=0.001). After adjustment for other stroke risk factors, women who used aspirin frequently or infrequently at study entry had a 1.8-fold (95% CI, 1.2 to 2.8) and 1.6-fold (95% CI, 0.9 to 3.0) increased risk of ischemic stroke, respectively (P<0.01, test for trend), compared with nonusers. In men, aspirin use was not statistically significantly associated with stroke risk. Findings were similar when aspirin use in the years before the incident stroke was used in the modeling. Aspirin use at entry was also associated with a 4-fold (95% CI, 1.6 to 10.0) increase in risk of hemorrhagic stroke for both infrequent and frequent users of aspirin (P=0.003). CONCLUSIONS: Aspirin use was associated with increased risks of ischemic stroke in women and hemorrhagic stroke overall in this elderly cohort, after adjustment for other stroke predictors. The possibility exists of confounding by reasons for aspirin use rather than cause and effect. Whether regular aspirin use increases stroke risk for elderly people without cardiovascular disease can only be determined by randomized clinical trials.

Aged↗
PubMed1998

Antithrombin cambridge II (Ala384Ser): clinical, functional and haplotype analysis of 18 families.

Thirty-one individuals from 18 unrelated families with antithrombin deficiency have been identified as having a single point mutation within codon 384 (13268 GCA-->TCA) resulting in an alanine to serine substitution. Six families (11 individuals) were identified by the screening of individuals with thromboembolic disease or with a family history of thromboembolic disease, whilst the remaining 12 families (20 individuals) were identified by screening of asymptomatic blood donors. Four individuals had a history of venous thrombotic disease, a further 2 gave a history of superficial thrombophlebitis but the remaining 25 individuals were asymptomatic. Affected individuals demonstrated normal immunological levels of antithrombin but a decrease in anti-IIa activity in the presence of heparin. Haplotype analysis was used to examine the possibility of a founder effect to explain the high frequency of this non-CpG mutation. 29/31 individuals showed a single common "core" haplotype, the only variation existing in the number of copies of an (ATT)n repeat polymorphism--13, 14, 15 or 17. The results suggest that at most there are four independent origins for this mutation.

Alanine↗
PubMed1998

A novel mutation in intron K of the PROS1 gene causes aberrant RNA splicing and is a common cause of protein S deficiency in a UK thrombophilia cohort.

In the course of investigating the molecular basis of protein S deficiency in 31 index cases with thrombophilia, we identified seven kindred where the underlying defect was a novel A to G transition 9 bp upstream of exon 12 in intron K of the PROS1 gene. In all but one case, the mutation caused type I deficiency. One individual had type III deficiency. While ectopic transcript analysis using the BstXI dimorphism in exon 15 failed to detect a transcript from the mutated allele, analysis of transcripts spanning exons 11 and 12 revealed a minor mRNA species. Sequencing confirmed the mutation created a new RNA acceptor site introducing 8 nucleotides of intronic sequence into the mature mRNA. Haplotype analysis of the defective PROS1 alleles in six families revealed the same haplotype in all affected individuals suggesting the presence of a common ancestor. Six of the fourteen relatives with the mutation experienced at least one venous thrombotic event strongly supporting the association of the mutation with venous thrombosis.

Alleles↗
PubMed1997

Co-inheritance of the 20210A allele of the prothrombin gene increases the risk of thrombosis in subjects with familial thrombophilia.

The presence of the 20210A allele of the prothrombin (PT) gene has recently been shown to be a risk factor for venous thromboembolism. This is probably mediated through increased plasma prothrombin levels. The aim of this study was to compare the prevalence of the prothrombin 20210A allele in control subjects and in subjects with recognised thrombophilia and to establish whether the additional inheritance of the PT 20210A allele is associated with an increased risk of venous thromboembolism. 101 subjects with a history of venous thromboembolism and diagnosed as having either factor V Leiden (R506Q) or heritable deficiencies of protein C, protein S or antithrombin were studied. The prevalence of the PT 20210A allele in this group was compared with the results obtained for 150 control subjects. In addition, the relationships were examined between genetic status and the number of documented thromboembolic episodes, and between plasma prothrombin levels and possession of the PT 20210A allele. 8 (7.9%) of the 101 patients were also heterozygous for the PT 20210A allele. This compares with 0.7% in the control subjects (p = 0.005). After exclusion of patients on warfarin, the mean plasma prothrombin of 113 subjects without 20210A was 1.09 U/ml, as compared with 1.32 U/ml in 8 with the allele (p = 0.0002). Among the 101 patients with either factor V Leiden, protein S deficiency, protein C deficiency or antithrombin deficiency, the age adjusted mean (SD) number of venous thromboembolic episodes at diagnosis was 3.7 (1.5) in those with the PT 20210A allele, as compared with 1.9 (1.1) in those without (p = 0.0001). We have demonstrated that the prevalence of the PT 20210A allele is significantly greater in subjects with venous thrombosis and characterised heritable thrombophilia than in normal control subjects and that the additional inheritance of PT 20210A is associated with an increased risk of venous thromboembolism. We have also confirmed that plasma prothrombin levels are significantly greater in subjects possessing the PT 20210A compared with those who do not.

Adolescent↗
PubMed1996

Molecular basis of protein S deficiency in three families also showing independent inheritance of factor V leiden.

The molecular basis of type I or III Protein S deficiency has been investigated in three kindred also showing independent inheritance of factor V (FV) Leiden. A T to C transition in codon 570 (Met-->Thr) was identified in the propositi and shown to segregate with protein S deficiency in all but one of the affected members of two kindred. This individual was heterozygous for a second transition (C to T) causing substitution of serine 624 by leucine. A second member of the same family, with markedly reduced free protein S levels when compared with affected relatives, was heterozygous for both mutations. Haplotype analysis of individuals with the mutated ATG570ACG allele in the two kindred suggested they may have been related by a common ancestor. A G to A transition resulting in substitution of cysteine 145 by tyrosine was detected in the third kindred. All mutations are believed to interfere with protein S binding to C4b-binding protein resulting in reduced free protein S levels. Of the five individuals studied who had experienced thrombotic events, three had combined protein S deficiency and FV Leiden reemphasising the importance of FV Leiden as an additional risk factor for thrombosis in protein S deficiency.

Alleles↗
PubMed1996

Cervical spondylosis: three-dimensional gradient-echo MR with magnetization transfer.

PURPOSE: To compare a three-dimensional Fourier transform (3DFT) gradient-echo pulse sequence with magnetization transfer at a short echo time against standard 3DFT gradient-echo technique in the evaluation of cervical spondylosis, specifically addressing the effects of motion and susceptibility artifacts on the dimensions of the neural foramina and contrast at the cerebrospinal fluid (CSF)-spinal cord interface. METHODS: Ten patients with clinically suspected cervical spondylosis were examined with axial MR imaging using both our standard 3DFT gradient-echo sequence and a 3DFT gradient-echo sequence with a short echo time plus magnetization transfer. Two neuroradiologists measured the transverse dimensions of 22 diseased neural foramina and graded the contrast at the CSF-spinal cord interface. RESULTS: Sixteen of 22 affected neural foramina were larger in the transverse dimension when the magnetization transfer technique was used than when the standard 3DFT gradient-echo sequence was used. In 9 of 10 patients superior contrast was seen at the CSF-spinal cord interface on images obtained with the magnetization transfer technique. CONCLUSIONS: In the cervical spine, 3DFT gradient-echo imaging with magnetization transfer improves contrast and sharpness of the CSF-spinal cord interface at short echo times. This results in less exaggeration of the neural foraminal stenosis as compared with that seen with standard 3DFT gradient-echo techniques owing to the diminished effects of motion and susceptibility artifacts.

Cerebrospinal Fluid↗
PubMed1994

High prevalence of a mutation in the factor V gene within the U.K. population: relationship to activated protein C resistance and familial thrombosis.

Recent findings have indicated the importance of factor V (FV) in causing resistance to activated protein C (APC) in a high proportion of patients with venous thrombosis. This prompted us to investigate whether resistance could be due to defective inactivation of FVa by APC. Consequently, we amplified a 3.2 kb fragment of the FV gene sequence encoding the heavy chain APC cleavage site. DNA analysis showed a guanine to adenine transition at nucleotide 1691 in all affected members of two families with inherited APC resistance associated with thrombosis and confirmed suspected homozygosity in two individuals. The mutation, in heterozygous form, was also found in approximately 3.5% of our normal population (n = 144) and correlated with low APC resistance. The high prevalence of this mutation suggests that it may be a major contributory factor in early thrombosis.

Base Sequence↗